volasertib (NBL-001) / Boehringer Ingelheim, Oncoheroes, Notable Labs - LARVOL DELTA

Synergistic suppression of hepatocellular carcinoma cancer stem cells by combined curcumin and PLK1 inhibition (AACR 2026) - "CSC spheres were treated with curcumin, the selective PLK1 inhibitor volasertib, or the combination... The combined use of curcumin and PLK1i exerts a powerful synergistic effect in suppressing hepatocellular carcinoma CSCs in vitro and in vivo. These findings support a promising therapeutic strategy integrating a traditional medicine-derived compound with a targeted inhibitor and warrant further preclinical and clinical development."

Cancer stem • Hepatocellular Cancer • Oncology • Solid Tumor • CASP3 • CASP9 • CD133 • NANOG • POU5F1 • SOX2

Investigating FOXC2-dependent mechanisms regulating stem cell Identity in breast cancer (AACR 2026) - "Pharmacologic PLK1 inhibition (Volasertib) reduces FOXC2 protein levels, and this loss is reversed by the proteasome inhibitor MG132, suggesting that PLK1-dependent phosphorylation stabilizes FOXC2. Live-cell imaging further indicates that FOXC2 is spatially regulated during mitosis and that phosphorylation may affect its chromatin association and inheritance. Collectively, our findings suggest PLK1-dependent phosphorylation of FOXC2 may stabilize the FOXC2 protein and influence its function during mitosis and regulate stem cell identity in daughter cells during cell division."

Breast Cancer • Embryonal Tumor • Oncology • Solid Tumor • Triple Negative Breast Cancer • FOXC2

Defining cancer initiating cells and their vulnerabilities in renal cell carcinoma (AACR 2026) - "Pharmacological blockade of PLK1 with Volasertib elicited dose-dependent inhibitory effect on spheroid and colony formation, with in-vivo validation showing that blocking PLK1 significantly delayed tumor growth and more efficiently prevented tumor formation in nude mice...Targeting PLK1 disrupts the fundamental self-renewal and tumor-initiating capacities of ccRCC, offering a promising avenue for therapeutic intervention through PLK1 inhibition. Furthermore, our data uncover novel and non-canonical functions for PLK1, which upon further characterization may open new ways for combinational therapeutic strategies involving PLK1 and its effectors with standard of care in advanced ccRCC."

Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • FOXM1

Targeting PLK1 or WEE1 uncovers a therapeutic vulnerability in BRCA1/2 wild-type, homologous recombination-proficient high-grade serous ovarian cancer (AACR 2026) - "We aimed to determine whether inhibition of PLK1 or WEE1, two G2/M checkpoint kinases, could uncover a therapeutic vulnerability in BRCA-WT/HRP HGSOC. We evaluated the effects of the PLK1 inhibitor volasertib and the WEE1 inhibitor adavosertib in BRCA-WT/HRP (and BRCA-mutant/HR-deficient (HRD) ovarian cancer models. BRCA-WT/HRP HGSOC exhibits distinct susceptibility to PLK1 or WEE1 inhibition through disruption of HR repair and mitotic regulation, revealing a DNA repair-based vulnerability not observed in BRCA-mutant/HRD tumors. These findings provide a strong rationale for biomarker-guided development of PLK1 or WEE1 inhibitors as therapeutic strategies for HRP ovarian cancers, a patient population with significant unmet clinical needs."

High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • PLK1 • RAD51 • TP53BP1

Discovery of Small Molecule Inhibitors against Polo-Like Kinase 1 Targeting Breast Cancer. (PubMed, Anticancer Agents Med Chem) - "These research findings established silymarin as a potential alternative drug targeting PLK1, which is highly expressed in HER2-positive breast cancer, and modulates the oncogenic processes not just in breast cancer, but also in other cancers."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PLK1

PLK1 Inhibition by Volasertib Suppresses Key Transcriptional Regulators Underlying Fibroblast Activation and Pulmonary Fibrosis. (PubMed, Am J Physiol Lung Cell Mol Physiol) - "In vivo, volasertib treatment attenuated fibroblast activation and collagen deposition during TGFα-induced pulmonary fibrosis. Together, these findings identify a pathogenic role for the WT1-MYCN-PLK1 axis in fibroblast activation and provide proof-of-concept evidence supporting PLK1 inhibition with volasertib as a potential therapeutic strategy for IPF."

Journal • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Nephrology • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Wilms Tumor • MYCN • PLK1 • TGFA • WT1

PLK1 or WEE1 inhibition targets homologous recombination repair proficiency in BRCA1/2 wild-type high-grade serous ovarian cancer. (PubMed, Cell Death Dis) - "We evaluated cell cycle-targeted strategies to overcome HR-proficient chemoresistance using either volasertib (a selective PLK1 inhibitor) or adavosertib (a potent WEE1 inhibitor) in BRCA-WT/HR-proficient and BRCA-mutant/HR-deficient HGSOC models. Functional and xenograft models confirmed selective vulnerability of BRCA-WT tumors to either PLK1 or WEE1 inhibition. Our work highlights a mechanistic framework linking cell cycle checkpoint inhibition to DNA repair pathway selectivity, providing a rationale for targeting mitotic regulators in HR-proficient ovarian cancer-a subgroup with high clinical unmet need."

Journal • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA • BRCA1 • BRCA2 • HRD • PLK1 • RAD51

Prediction of Volasertib Sensitivity in Acute Myeloid Leukemia Relapsed or Refractory to Venetoclax Plus Azacitidine (ASH 2024) - "A randomized phase 2 trial in acute myeloid leukemia (AML) in the first line (1L) setting with the polo-like kinase 1 (PLK1) inhibitor volasertib (Vola) in combination with low-dose cytarabine (LDAC) yielded a 31.0% CR + CRi rate and a median overall survival (OS) of 8.0 months in contrast to 13.3% and 5.2 months, respectively, for LDAC without volasertib...Notable Labs has received US FDA clearance to test volasertib in combination with decitabine in a phase 2 clinical trial in relapsed/refractory (R/R) AML...Ven-refractory AML has no standard of care for treatment and portends dismal outcomes in patients. The encouraging performance of our ex vivo predictive medicine platform could pave the way for improving Vola response rates in patients in the upcoming phase 2 volasertib study."

Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • TP53

Long-term functional drug and immunotherapy screening in immune-competent patient-derived microtissues across brain tumors (SNO 2025) - "Glioma cell line-based screens revealed inter-model variability in drug sensitivity, with only a few agents, including Pimasertib, Etoposide, Buparlisib, and Volasertib, demonstrating consistent efficacy, underscoring the need for individualized profiling. Our long-term, dynamic screening system supports personalized oncology approaches by enabling functional analysis of both drug and immune responses. Further validation in prospective clinical trials is required to determine its translational impact."

Clinical • Brain Cancer • Glioblastoma • Glioma • Meningioma • Oncology • Solid Tumor

Long-term functional drug and immunotherapy screening in immune-competent patient-derived microtissues across brain tumors (WFNOS 2025) - "Glioma cell line-based screens revealed inter-model variability in drug sensitivity, with only a few agents, including Pimasertib, Etoposide, Buparlisib, and Volasertib, demonstrating consistent efficacy, underscoring the need for individualized profiling. Our long-term, dynamic screening system supports personalized oncology approaches by enabling functional analysis of both drug and immune responses. Further validation in prospective clinical trials is required to determine its translational impact."

Clinical • Brain Cancer • Glioblastoma • Glioma • Meningioma • Solid Tumor

PLK1 AS A VULNERABLE TARGET OF BAP1-DRIVEN UNDIFFERENTIATED PLEOMORPHIC SARCOMAS (CTOS 2025) - "We determined that Bap1 is a potent tumor suppressor of UPS. Our findings pave the way for translating volasertib as a targeted therapy to treat patients with Bap1-driven UPS, a group currently lacking treatment option."

Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Undifferentiated Pleomorphic Sarcoma • BAP1 • PLK1 • TP53

A Phase 2 Study with Volasertib for Ven-HMA Relapsed/Refractory Acute Myeloid Leukemia Patients Guided By a Predictive Precision Medicine Platform (ASH 2023) - "A BI Phase 2 study showed volasertib combined with low-dose cytarabine (V+LDAC) delivered a complete response (CR) + CR with incomplete count recovery (CRi) rate of 31. Secondary endpoints include an assessment of the diagnostic performance characteristic of Notable's drug sensitivity score in predicting in vivo volasertib clinical response. Specific strategies, including tailored dosing, robust infection control, and carefully selecting drug combination partners are designed to mitigate the adverse events observed in BI's Phase 3 trial and maximize volasertib's therapeutic impact regarding both efficacy and safety."

Clinical • P2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Oncology • Pediatrics • PLK1

Polo-like Kinase 1 Activation Regulates Angiotensin II-Induced Contraction in Pudendal and Small Mesenteric Arteries from Mice. (PubMed, Cells) - "We then investigated whether PLK1 regulates SMC contractility induced by phenylephrine (PE), U46619, and angiotensin II (Ang II) in arteries, and by PE, serotonin (5-HT), and electrical field stimulation (EFS; 1-16 Hz) in the CC, both in the presence and absence of the PLK1 inhibitor volasertib...These results suggest that PLK1 selectively mediates contraction in response to Ang II and neurogenic stimuli. PLK1 may therefore represent a novel, stimulus-specific regulator of vascular and erectile smooth muscle contractility."

Journal • Preclinical • PLK1

PLK1 Acts in Homologous Recombinatorial Repair and in Mitosis As Synthetically Lethal with the Fanconi Anemia/BRCA Pathway (ASH 2024) - "Drugs : PLK1 inhibitor (volasertib), PARP1 inhibitor (olaparib), Mitomycin C (MMC) TCGA : Analysis of PLK1 and FANCD2 expression levels to score HR repair efficiency, disease prognosis in HPV-neg HNSCC, PLK1 expression in all cancer types, co-mutation mutation rate of FA and PLK1 genes. Conclusion : PLK1 is synthetic lethal in the FA pathway, the targeting of which is caused by disruption of its HR and mitotic function. Such a strategy can be combined with low dose treatment with crosslinkers or with of PARP1 inhibitors."

Synthetic lethality • Anemia • Aplastic Anemia • Head and Neck Cancer • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Lymphoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • BRCA • BRCA2 • FANCA • FANCD2 • PLK1 • RAD51

Neutrophil/Leukemia-Tropic Dual-Drug Nanomedicine Potentiates the Treatment of Acute Myeloid Leukemia. (PubMed, Adv Mater) - "Here, a neutrophil/leukemia-tropic polymersome vincristine/volasertib dual-drug nanoformulation (NLP-Vi/Vo) is reported to selectively bind to leukemia cells and neutrophils, and to ratiometrically release clinical chemotherapeutics and a polo-like kinase 1 inhibitor, thereby potentiating the treatment of AML. NLP-Vi/Vo shows excellent therapeutic efficacy in malignant murine AML and human AML xenograft models. Collectively, neutrophil/leukemia-directing dual-drug nanomedicines offer a promising treatment strategy for AML."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • PLK1

PLK1 INHIBITION OFFERS A CLINICALLY RELEVANT STRATEGY FOR DIPG WITH TP53-DEPENDENT THERAPEUTIC SYNERGY (SIOP 2025) - "We evaluated the efficacy of PLK1 inhibition using BI-2536, volasertib, and onvansertib in patient-derived DIPG models, with a focus on TP53 status, pharmacokinetics, and synergy with RT...Co-treatment with vinorelbine significantly increased volasertib CNS accumulation to ~57 nM (p=0.0021), potentiating a combinatorial therapeutic strategy... PLK1 inhibition shows strong anti-tumour activity in DIPG and synergises with RT in TP53-deficient models. These findings support biomarker-guided PLK1-targeted strategies and highlight the need to optimise CNS delivery for clinical translation."

Clinical • Brain Cancer • Diffuse Intrinsic Pontine Glioma • Glioma • Pediatrics • Solid Tumor • PLK1 • TP53

FUNCTIONAL PRECISION MEDICINE REVEALS DRUG VULNERABILITIES IN PEDIATRIC SARCOMA (SIOP 2025) - "All tested RMS cell lines, including PAX3::FOXO1 fusion-positive RH30, were sensitive to PLK1 inhibitor volasertib (sDSSf ≥10). Filanesib, a mitotic inhibitor under clinical investigation, showed broad activity in RMS cell lines...Here, the primary tumor PDCs were responsive to carboplatin, decitabine, selumetinib, and RET inhibitor pralsetinib, while metastatic PDCs showed sensitivity to selumetinib, bortezomib, and vinorelbine. Conclusions As a conclusion, this study demonstrates that DSRT of patient-derived sarcoma cells, supported by well-defined control models, enables the identification of actionable drug sensitivities. Integrating FPM with next-generation sequencing may enhance personalized treatment strategies in pediatric sarcoma."

Clinical • Tumor mutational burden • Pediatrics • Rhabdomyosarcoma • Sarcoma • Solid Tumor • FOXO1 • PAX3 • PAX7 • TMB

Human Retinal Organoid Modeling Defines Developmental Window and Therapeutic Vulnerabilities in MYCN-Amplified Retinoblastoma. (PubMed, Int J Mol Sci) - "Pharmacological screening further identified distinct therapeutic vulnerabilities, demonstrating distinct subtype-specific sensitivity of MYCN-driven cells to transcriptional inhibitors (THZ1, Flavopiridol) and the cell-cycle inhibitor Volasertib, indicative of a unique oncogene-addicted state compared to RB1-deficient retinoblastoma cells. Collectively, our study elucidates the developmental and molecular mechanisms underpinning MYCN-driven retinoblastoma, establishes a robust and clinically relevant human retinal organoid platform, and highlights targeted transcriptional inhibition as a promising therapeutic approach for this aggressive pediatric cancer subtype."

Journal • Eye Cancer • Oncology • Pediatrics • Retinal Disorders • Retinoblastoma • Solid Tumor • MYCN • RB1 • SOX2

The status of p53 affects the efficacy of PLK1 inhibitor BI6727 in prostate cancer cells. (PubMed, Front Cell Dev Biol) - "Mechanistically, BI6727 reduces the degradation of Topors, thereby increasing the stability of p53 by reducing its ubiquitination. This ultimately influences the sensitivity of prostate cancer cells with different p53 statuses to BI6727.In summary, this study identifies p53 as a key factor limiting the clinical efficacy of BI6727 in prostate cancer cells."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • Targeted Protein Degradation

Investigation of ribociclib, abemaciclib and palbociclib resistance in ER+ breast cancer cells reveal potential therapeutic opportunities`. (PubMed, Sci Rep) - "CDK4/6i-resistant cell lines (MCF7rR, MCF7rA, MCF7rP, T47DrR, T47DrA, and T47DrP) were isolated and evaluated for their aggressive phenotypes, cross-resistance, transcriptomic changes, and sensitivity to volasertib (PLK1 inhibitor) and barasertib (AukB inhibitor). We conclude that cell cycle upregulation leading to G2/M progression is a key route for CDK4/6i resistance. AukB or PLK1 inhibitors that block G2/M phase could be a promising strategy."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • CDK6 • CDKN2B • ER • HER-2 • TGFB1

Ursolic acid affects autophagy and apoptosis of breast cancer through PLK1 via AKT/mTOR signaling pathway. (PubMed, Med Oncol) - "Tamoxifen (TAM) and adriamycin (ADM) served as positive control agents. HE staining demonstrated significant necrosis, while IHC/WB analysis validated that UA or UA combined with Volasertib may reduce levels of Bcl-2, PLK1, p-AKT/AKT, and p-mTOR/mTOR, in conjunction with increased LC3 II/I. In conclusion, the study revealed that UA may affect the apoptosis and autophagy of breast cancer through PLK1 via AKT/mTOR signaling pathway."

IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • Transplantation • Women's Health • BCL2 • PLK1

In situ generation of anti-leukemia vaccine by immunogenic dual-drug nanomedicine and polymersomal CpG nanoadjuvant. (PubMed, J Colloid Interface Sci) - "Herein, we report the facile in situ generation of an anti-AML vaccine via an immunogenic vincristine/volasertib dual-drug nanomedicine (nanoVi/Vo) and a polymersomal CpG immunoadjuvant (nanoCpG). Notably, nanoVi/Vo combined with nanoCpG substantially suppressed leukemia progression in the bone marrow and infiltration to other organs, resulting in a significant survival benefit, with 57% of the mice surviving. This in situ vaccine generation strategy has promising potential as an effective immunotherapy approach for AML."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

COG133 peptide-conjugated lipid nanoparticles sensitize medulloblastoma to radiation therapy in mice. (PubMed, J Control Release) - "In this study, we aimed to decrease the dose of irradiation and the proliferation of MB by using Volasertib (VSB), a Polo-like kinase 1 (PLK1) specific inhibitor. Furthermore, COG133-LNPs along with irradiation decreased tumor burden significantly as compared to VSB or radiation alone. To our observation, COG133-LNPs display high potency in killing MB cells and sensitizing them toward radiation therapy."

Journal • Preclinical • Brain Cancer • Cognitive Disorders • Developmental Disorders • Medulloblastoma • Oncology • Solid Tumor • PLK1

Vincristine/Volasertib Polymersome Injection Enables High-Efficiency Synergistic Treatment of Acute Lymphoblastic Leukemia. (PubMed, Acta Biomater) - "Compared with free VCR/Vol, VCR/Vol polymersomes with tailored drug ratios substantially inhibited leukemia progression in both cell line- and patient-derived orthotopic ALL models without inducing toxicity, leading to a significant survival benefit. This synergistic polymersome injection may provide a powerful and safe combination therapy for ALL patients."

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • PLK1

Deep transfer learning approach for automated cell death classification reveals novel ferroptosis-inducing agents in subsets of B-ALL. (PubMed, Cell Death Dis) - "Importantly, using several leukemia models, we determined that volasertib delayed tumor growth and induced ferroptosis in vivo. Taken together, we have applied DTL to automated live-cell imaging in pharmacological screening to identify novel ferroptosis-inducing functions of a clinically relevant anti-cancer therapeutic."

Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology